Throughout life, the nervous system acquires and maintains many different motor skills. How this is accomplished is one of the central problems of neuroscience research. In the past, the challenge was to discover examples of CNS plasticity accompanying skill acquisition. Now, many kinds of plasticity are known to occur continually throughout the CNS, and the challenge is to understand how this complex plasticity accounts for motor skills and how this plasticity may be guided so as to restore useful function after injury or disease. This requires models based on simple skills produced by defined and accessible neural circuitry. The spinal stretch reflex (SSR or tendon jerk) satisfies this requirement. Its spinal pathway is influenced by the brain. By changing this influence in response to an operant conditioning protocol, monkeys, humans, rats, and mice can gradually increase or decrease the SSR or its electrical analog, the H-reflex. According to the standard definition of "skill" as "an adaptive behavior acquired through practice," this reflex change is a simple motor skill. This laboratory is defining the plasticity that underlies this skill and is learning how the plasticity can be guided to help restore motor function after spinal cord injury and in other disorders. The work of the past grant period showed that sensorimotor cortex (SMC) and its corticospinal tract (CST) output have a key role in H-reflex conditioning, and that H-reflex conditioning can improve locomotion after spinal cord injury. Based on this work, this proposal will test the hypotheses that: (1) specific changes in SMC neuronal activity precede and lead the changes in the H-reflex;and (2) therapeutic interventions that improve motor function by changing H-reflex size do so by changing SMC activity. The next grant period will evaluate these hypotheses: by defining the changes in SMC activity that precede and accompany soleus H-reflex conditioning;and by showing that therapeutic interventions that change H-reflex size cause changes in SMC activity that underlie the changes in H-reflex size and the associated functional improvements, and that these functional improvements persist after H-reflex conditioning ends. These aims will be addressed by studying SMC neuronal activity, H-reflexes, and locomotor function before, during, and after up-conditioning or down-conditioning of the soleus H-reflex in normal rats and in rats with spinal cord lesions that create locomotor abnormalities. The results should reveal the neuronal mechanisms by which the SMC induces and maintains the plasticity responsible for a simple motor skill. They should also spur development of new protocols that modify SMC neuronal activity so as to induce and guide spinal cord plasticity to help restore useful function after spinal cord injury or with other CNS damage or disease. PUBLIC HEALTH RELEVANCE Motor skills are acquired and maintained throughout life by changes in both the brain and the spinal cord. This project will use a simple laboratory model to learn how these changes interact to support motor skills. This work should lead to new methods for inducing changes in brain and spinal cord that help to improve motor function after spinal cord injury or in other disorders.